Related Experiment Video
Updated: Jun 23, 2026
A Familial Hypercholesterolemia Human Liver Chimeric Mouse Model Using Induced Pluripotent Stem Cell-derived Hepatocytes
Published on: September 15, 2018
Influence of LDL-receptor mutation type on age at first cardiovascular event in patients with familial
Olga W Souverein1, Joep C Defesche, Aeilko H Zwinderman
1Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, PO Box 22700, 1100 DE Amsterdam, the Netherlands. o.w.souverein@amc.uva.nl
Insights
In familial hypercholesterolaemia (FH), LDL-C levels significantly impact cardiovascular event risk more than LDL-receptor (LDLR) gene mutation type. This finding is crucial for managing FH patients.
Area of Science:
- Cardiovascular Genetics
- Metabolic Disorders
- Pharmacogenomics
Background:
- Familial hypercholesterolaemia (FH) is a genetic disorder characterized by high LDL cholesterol (LDL-C).
- The LDL-receptor (LDLR) gene plays a critical role in cholesterol metabolism.
- Understanding the impact of LDLR mutations on cardiovascular events is vital for patient management.
Purpose of the Study:
- To determine how different LDL-receptor (LDLR) gene mutations influence the age of first cardiovascular event in patients with familial hypercholesterolaemia (FH).
Main Methods:
- Retrospective cohort study of 862 Dutch FH patients with known LDLR mutations.
- Gamma frailty Cox models analyzed event-free survival, including covariates like hypertension, smoking, and lipid levels.
- Mixed effects models assessed the association between LDLR mutation type and lipid levels.
Main Results:
- A total of 86 distinct LDLR mutations were identified in the cohort.
- Twenty-two percent of patients experienced a cardiovascular event, with a median age of 47.1 years.
- LDLR mutation type significantly affected LDL-C levels but not HDL cholesterol levels. The mutation type's effect on event-free survival was only significant when LDL-C levels were excluded from the model.
Conclusions:
- LDL-C levels are a more significant predictor of event-free survival in FH patients than the specific type of LDLR mutation.
- These findings highlight the primary importance of managing LDL-C levels in FH patients, irrespective of the specific LDLR mutation.
- Further research may explore the interplay between LDLR mutation severity and therapeutic interventions.
Aims:
To investigate the influence of different LDL-receptor (LDLR) gene mutations on age at first cardiovascular event in familial hypercholesterolaemia (FH) patients.
Methods And Results:
Dutch FH patients (n = 862) with known LDLR mutations from a retrospective cohort study were included. A gamma frailty Cox model was used. An event was defined as the first cardiovascular event. Gender, hypertension, smoking, diabetes, HDL cholesterol, LDL cholesterol (LDL-C), or triglycerides were included as covariates. Furthermore, the effect of LDLR mutation type on LDL and HDL cholesterol levels was investigated using mixed effects models, including gender, smoking, body mass index, and age at time of lipid measurement as covariates. A total of 86 different LDLR mutations were present in this cohort. Twenty-two percent of patients experienced an event (median age: 47.1 year; range: 25.6-85.8 years). The effect of LDLR mutation type on event-free survival is only significant in the models without LDL-C levels. Also, LDLR mutation type was significantly associated with LDL-C levels (P = 0.007), but not with HDL cholesterol levels (P = 0.12).
Conclusion:
In the present study, LDL-C levels are a more important risk factor of event-free survival than the type of LDLR mutation.
Related Concept Videos
01:38Inflammation
01:29Cholesterol: Significance and Regulation
Considering cholesterol and...
01:29Pharmacogenomics: Identification of New Drug Targets
01:30Coronary Artery Disease I: Introduction
01:30Atherosclerosis I: Introduction
01:26Atherosclerosis III: Management